Receptor mediated uptake of a radiolabeled contrast agent sensitive to β-galactosidase activity

Alauddin, Mian M.; Louie, Angelique Y.; Shahinian, Antranik; Meade, Thomas J.; Conti, Peter S.

doi:10.1016/s0969-8051(02)00392-x

Cited by 35 publications

(35 citation statements)

References 12 publications

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“…Moreover, the cell densities used for these studies is on the order of that found for macrophages in isolated human plaques, indicating that these imaging results will be applicable to the in vivo case. (52)(53)(54)(55)(56) There are number of examples in the literature of efficient cellular uptake of Gd(III) complexes using Gd-DOTA derived molecules (57)(58)(59)(60). More recent efforts have sought to maximize the load of Gd delivered per receptor by tethering carrier molecules to dendridic polymers containing high numbers of Gd(III)(61), uptake through the folate receptor has been demonstrated by this means as has avidin-biotin antibody-based targeting (59,62,63).…”

Section: Resultsmentioning

confidence: 99%

Development of Contrast Agents Targeted to Macrophage Scavenger Receptors for MRI of Vascular Inflammation

2006

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Atherosclerosis is a leading cause of death in the U.S. Because there is a potential to prevent coronary and arterial diseases through early diagnosis, there is a need for methods to image arteries in the subclinical stage as well as clinical stage using various non-invasive techniques, including Magnetic Resonance Imaging (MRI). We describe a development of a novel MRI contrast agent targeted to plaques that will allow imaging of lesion formation. The contrast agent is directed to macrophages, one of the earliest components of developing plaques. Macrophages are labeled through the macrophage scavenger receptor A, a macrophage specific cell surface protein, using an MRI contrast agent derived from scavenger receptor ligands. We have synthesized and characterized these contrast agents with a range of relaxivities. In vitro studies show that the targeted contrast agent accumulates in macrophages and solution studies indicate that micromolar concentrations are sufficient to produce contrast in an MR image. Cell toxicity and initial biodistribution studies indicate low toxicity, no detectable retention in normal blood vessels, and rapid clearance from blood. The promising performance of this contrast agent targeted towards vascular inflammation opens doors to tracking of other inflammatory diseases such as tumor immunotherapy and transplant acceptance using MRI.

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Section: Resultsmentioning

confidence: 99%

Development of Contrast Agents Targeted to Macrophage Scavenger Receptors for MRI of Vascular Inflammation

2006

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“…111 In]-radiolabeled galactopyranosyl conjugate of DOTA for scintigraphic applications using the targeting of the ASGP-R both in hepatic cell lines and mice had appeared in the literature [37].…”

Section: Mri Contrast Agentsmentioning

confidence: 99%

“…Compound 42 was shown to be useful for in vitro and in vivo (Xenopus laevis embryos) visualization and localization of gene expression by MRI [69]. However, results from the biodistribution of the analogue 111 In(III)-radiolabeled compound in mice revealed that most of the tracer was located in the liver (taken up by ASGP-R) already, 2 h postinjection [37]. This approach was further exploited in the development of in vitro assays for the determination of the activity of b-glucuronidase [70], an enzyme with enhanced extracellular concentration around tumors and involved in the liberation of b-glucuronic acid during the mono-prodrug therapy.…”

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confidence: 99%

Glycoconjugate Probes and Targets for Molecular Imaging Using Magnetic Resonance

2010

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Review Molecular recognition of sugar residues applied in molecular imagingMolecular imaging aims at probing the molecular abnormalities that are the basis of diseases rather than to image their effects [1]. An important prerequisite of this approach is the selection of appropriate markers of disease and of targeting vectors to recognize them. The latter can include low-molecular weight substrates for enzymes or high-molecular weight affinity ligands, such as monoclonal antibodies, hormone analogs and recombinant proteins. Of the three major classes of biomolecules (proteins, nucleic acids and carbohydrates), the latter class is the least exploited in molecular imaging. However, a dense layer of glyco conjugates covers all cells and carbohydrate mediated cellular recognition plays an important role in nature, both in normal and malignant processes, such as cell-cell communication, infection, inflammation, metastasis and reproduction. As carriers of information, the carbohydrates have far greater potential than proteins and nucleic acids; three different nucleotides or amino acids can generate only six distinguishable structures, while over 1000 structures can be built up from three different monosaccharides [2]. This level of complexity is probably the reason for the fact that the exploration of these compounds in molecular imaging is lagging behind [3]. Recently, significant progress has been made in glycochemistry and glycobiology; for example, automated solid-phase synthesis of oligo saccharides has become possible [4], carbohydrate-based vaccines have been developed [5] and high-throughput methods have been designed for the screening of molecular interactions [6]. The exciting new developments in glycoscience are opening way for new challenges in exploring the full potential of carbohydrates in molecular imaging. Therefore, here we give an overview of the recent literature on the use of glycoconjugates either as probes or targets in molecular imaging using MRI.MRI contrast agents (CAs) are broadly described as positive or negative, depending on whether they give rise to a brightening or a darkening effect on the MR image, respectively. The positive or brightening effect predominantly relates to the longitudinal proton relaxation time (T 1 ) and the negative or darkening effect predominantly relates to the transverse proton relaxation time (T 2 ). To date, the majority of commercially available and clinically applied positive CAs are Gd 3+ complexes of the polyaminocarboxylates diethylene triamine pentacetic acid (DTPA) and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) (see FiguRe 1 for some typical examples) and negative CAs are various iron oxide particles. These agents are not actively targeting. The targeted CAs for application in molecular imaging that are currently under development and described below are generally based on compounds 1 (Gd-DTPA) and 2 (Gd-DOTA), as well as iron oxide nanoparticles.Glycoconjugate probes and targets for molecular imaging using magnetic resonanceRecently...

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“…[52] The targeting of the ASGPR has been demonstrated both in a cell line and mice with a 111 In-radiolabelled galactopyranosyl conjugate of DOTA (1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane). [27] 99m Tc-DTPA-GSA, a conjugate of galactosylated serum albumin (GSA) with 99m Tc-DTPA (DTPA = 3,6,9-tris(carboxymethyl)-3,6,9-triazaundecan-1,11-dioic acid), is useful in SPECT (single photon emission computed tomography) hepatic imaging to assess ASGPR in mice [28] and used clinically in humans. [29,30] Monocrystalline iron oxide nanoparticles (MION) conjugated to the bovine plasma protein asialofetuin (ASF), (MION-ASF), [31] arabinogalactan (AG)-coated ultra-small superparamagnetic iron oxide particles (USPIO), (AG-USPIO), [32,33] spin-labelled arabinogalactan, [34] and a Gd-DTPA conjugate of polylysine (PL) derivatized with galactosyl groups (Gd-DTPA-gal-PL), [35] have also been developed as potential contrast agents for liver MRI by targeting the hepatocyte ASGPR and tested in cells and mice.…”

Section: Magnetic Resonance Imaging (Mri) Is a Diagnostic Modalitymentioning

confidence: 99%

Lanthanide(III) Complexes of DOTA–Glycoconjugates: A Potential New Class of Lectin‐Mediated Medical Imaging Agents

André

Geraldes

Martins

et al. 2004

Chemistry A European J

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Receptor mediated uptake of a radiolabeled contrast agent sensitive to β-galactosidase activity

Cited by 35 publications

References 12 publications

Development of Contrast Agents Targeted to Macrophage Scavenger Receptors for MRI of Vascular Inflammation

Development of Contrast Agents Targeted to Macrophage Scavenger Receptors for MRI of Vascular Inflammation

Glycoconjugate Probes and Targets for Molecular Imaging Using Magnetic Resonance

Lanthanide(III) Complexes of DOTA–Glycoconjugates: A Potential New Class of Lectin‐Mediated Medical Imaging Agents

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